864908-76-9Relevant articles and documents
Discovery of Novel UDP- N-Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against Pseudomonas aeruginosa
Andersen, Ole A.,Barbeau, Olivier R.,Barker, John,Cain, Ricky,Centrella, Paolo A.,Clark, Matthew A.,Compper, Christel,Corbett, David,Cuozzo, John W.,Dejob, Magali,Dejonge, Boudewijn L. M.,Deng, Boer,Dickie, Anthony P.,Dorali, Alain,Etheridge, Donnya,Evans, Sian,Faulkner, Adele,Gadouleau, Elise,Gorman, Timothy,Haase, Denes,Holbrow-Wilshaw, Maisie,Hunt, Avery,Keefe, Anthony D.,Krulle, Thomas,Li, Xianfu,Lumley, Christopher,Mertins, Barbara,Napier, Spencer,Odedra, Rajesh,Papadopoulos, Kostas,Parkes, Alastair L.,Roumpelakis, Vasileios,Ryan, M. Dominic,Sanzone, Angelo,Sigel, Eric A.,Southey, Michelle,Soutter, Holly T.,Spear, Kate,Stein, Daniel B.,Thommes, Pia,Trimby, Emily,Troast, Dawn M.,Williams, Jennifer,Zahn, Michael,Zhang, Ying
, p. 14377 - 14425 (2021/10/25)
This study describes a novel series of UDP-N-acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of Pseudomonas aeruginosa LpxA with no activity against Escherichia coli LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against P. aeruginosa LpxA (best half-maximal inhibitory concentration (IC50) 20 μM and MIC > 128 μg/mL). The mode of action of analogues was confirmed through genetic analyses. As expected, compounds were active against multidrug-resistant isolates. Further optimization of pharmacokinetics is needed before efficacy studies in mouse infection models can be attempted. To our knowledge, this is the first reported LpxA inhibitor series with selective activity against P. aeruginosa.
Synthesis of halogenated phenols by directed ortho-lithiation and ipso-iododesilylation reactions of O-aryl N-isopropylcarbamates
Kauch, Matthias,Hoppe, Dieter
, p. 1578 - 1589 (2007/10/03)
The regioselective synthesis of halogenated phenols via directed ortho-lithiation reactions of in situ N-silylated O-aryl N-isopropylcarbamates is reported. This protocol is complemented by ipso-iododesilylation reactions of C-silylated carbamates and iodine-magnesium exchange reactions, which are facilitated by the adjacent carbamoyl group. These methods provide an entry into a series of o-fluoro-, o-iodo-, and o,o′-diiodophenols in high yields which are otherwise difficult to obtain. Georg Thieme Verlag Stuttgart.
